Nucleic acid biosynthesis, regulation of genetic information, and radiation damage/repair proceed via electron transfer (ET) reactions, often involving transition metal complexes [1-6]. ET in these systems occurs over large distances, well beyond van der Waals contact. The fundamental ET mechanism is under intense current investigation, but remains the subject of substantial debate [7-10]. Experiments reported in the last five years appear to be in dramatic conflict [11-13]; the most basic question of how far and how fast electrons can travel between metal complexes attached to DNA remains open [14]. In instances of this kind, theory can play a particularly important role in unraveling apparent conflicts by charting the accessible mechanist regimes. More importantly, theory can help design new experiments that will provide the critical tests of proposed electron transfer mechanisms. The goal of this study is to employ modern methods of electronic structure theory and molecular dynamics simulation to place constraints upon how far and how fast electron transfer may proceed in DNA. The critical aims of this project are: (1) to determine how sensitive DNA electron transfer rates are to the energetics of the donor (D) and acceptor (A) redox active transition-metal groups and DNA sequence when the energy levels of donor and acceptor are far from the energies of the base pair levels, (2) to determine how sensitive DNA electron transfer rates are to the energetics of the donor and acceptor redox active transition-metal groups and DNA sequence when the energy levels of donor and acceptor are close to the energies of the base pair levels, (3) to determine how the rich dynamical fluctuations in three-dimensional DNA structure (including hydration) modulate the donor-acceptor interaction. This project will employ both semi-empirical [15] and linear scaling ab initio electronic structure methods [16,17] to compute the donor- acceptor electronic interaction. Molecular geometries used in these calculations will be sampled from molecular mechanics and classical molecular dynamics simulations. Finally, electron transfer reorganization energies will be calculated [18-20]. Taken together, these three investigations will be used to build a comprehensive theory of DNA electron tunneling processes, and should reveal the dependence upon donor/acceptor binding motif and energetics, , DNA sequence, and the dynamical fluctuations of the DNA structure.